The PC12 cell line is a cloned line derived from a rat pheochromocytoma that has proved to be a useful model system to study the regulation of neural development. A number of neural properties (neurotransmitter synthesis, neurite extension, enzyme induction, cell division and neurosecretion) are regulated by adenosine in PC12 cells. The major mediator of adenosine in these cells is cAMP. The central objective of this grant is to establish the roles of the cAMP-dependent kinases in regulation of neural properties in these cells. To do this, we will isolate mutants that are: defective in the regulation of cAMP production, defective in one or more of the cAMP-dependent protein kinases, or defective in a regulatory step subsequent to the activation of the cAMP-dependent protein kinases. We will establish the biochemical nature of the defect in these mutants and determine the effect of each mutation on the regulation of the differentiated properties of the cells by adenosine or cAMP analogues.